A Novel Nanomaterial/Hydrogel Composite for Soft Tissue Regeneration
31 August till 2 September 2016، Tehran - Iran
Presentation Type: Speech
Abstract: Objective: Elastic hydrogels carry the potential to serve as scaffolds for various biomedical applications. Though some elastic hydrogels are biocompatible, most of the synthetic polymer-based elastic scaffolds lack bioactive sequences to promote cell adhesion or migration, which is important for their application in tissue engineering. Alternatively, recombinant proteinbasedpolymers such as elastin-like polypeptides (ELPs) are biocompatible and have been widely investigated for biomedical applications. Photocrosslinkable, protein-based biomaterials provide controllable and biocompatible crosslinking, permitting their use as tissue scaffolds and surgical materials.
Materials and Methods: Engineered ELPs in this study were designed by recombinant expression in Escherichia coli (E. coli), followed by purification by inverse transition cycling. To fabricate the hydrogels, lyophilized ELPs were dissolved in phosphate-buffered saline (PBS) and photocrosslinked with UV light (360-480 nm wavelength, 850 mW) for 3 min. The swelling ratios of 10, 15 and 20% (w/v) ELP hydrogels were evaluated in PBS at 4°C and 37°C. Tensile and compressive cyclic tests were performed on ELP-based hydrogels using a mechanical tester (Instron model 5542) with a 10 N load cell. The in vivo biocompatibility of the ELP gel was investigated in a subcutaneous implantation model in rats. In addition, the use of nanoparticle-coated ELP hydrogel as a hemostatic material was evaluated in a rat liver bleeding model.
Results: Recombinantly expressed ELP hydrogels were shown to photocrosslink without additional modifications to the as-expressed protein sequence. The gels were extensible up to 420% strain and exhibited fatigue resistance in compression. The inclusion of thiol groups in expressed ELPs allowed for rapid photocrosslinking of hydrogels that maintained the elasticity and biocompatibility inherent in ELPs. The large extensibility of ELPs is important for the engineering of elastic tissues. The recombinant design of these ELPs allow for exceptional control over the presentation of bioactive peptide sequences, which can be used to improve cell viability, proliferation or promote specific cellular interactions in vitro or in vivo. In vivo examination revealed excellent biocompatibility, minimal degradation, and potential as hemostat scaffold when coated with silica particles.
Conclusion: The possibility for conjugation of bioactive sequences into recombinant proteins provides a wide range of tissue engineering applications that such a photocrosslinkable ELP could be tailored for, including cartilage regeneration, and vascular as well as ocular applications. Since crosslinking can be conducted in situ, the ELP can likewise function as tissue fillers, conforming to the shape of defects and subsequently being crosslinked stabilize the hydrogel.